A bovine adrenocortical cell culture system will be used to study changes in surface receptors during in vitro aging. These endocrine cells maintain the differentiated function of steroidogenesis. Cells respond to ACTH, PGE1, angiotensin II and fibroblast growth factor (FGF); an exponential decline in ACTH stimulated cAMP production during their finite life span in culture is associated with changes in ACTH control of steroidogenesis and cell replication. ACTH receptors will be quantitated to determine whether the decline in ACTH responsiveness during long-term proliferation results from a direct loss of receptor sites or from membrane alterations. Angiotensin II and FGF receptors, which are "growth" receptors in these cells, will be quantitated to determine whether slowing of cell growth in phase II aging is associated with a decline in "growth" receptors. Receptors will be compared to the effects of FGF and angiotensin II on the rate of entry of cells into the S phase of the cell cycle. Membrane ganglioside composition will be analyzed in cells of varying ages and compared to changes in receptors for ACTH, angiotensin II and FGF. Correction of any deficiencies noted will be attempted to see whether changes in functional receptors with cell age can be reversed. Receptor synthesis and turnover at different ages in response to desensitization, enzyme and chemical treatment will be studied. The effect of cell: cell interaction, nutrient, hormones, and antioxidants on changing receptors during cell aging in culture will be investigated. Control of both differentiated function and cell replication during aging depend on hormone/growth factor: receptor interactions; the bovine adrenocortical cell will be used to quantitate changes in receptors at different stages of the life span in culture and probe membrane changes underlying the functional alterations.